DNA Test for Drug Sensitivity in Dogs

In 1983 researchers first described a peculiar reaction in some Collies to ivermectin, a drug used for heartworm prevention, among other things. Although ivermectin can cause toxicity in any dog if you give enough of it, these Collies had neurological signs (drooling, stumbling, blindness, coma, respiratory problems and even death) at doses that were 1/200th of the dose needed to cause problems in other dogs. Nobody knew why.

Soon afterward, several other breeds, most of them related to Collies, showed similar symptoms. Over the next two decades researchers continued to search for the cause, and continued to draw blanks. Now, thanks to research at Washington State University, we finally know.

The problem can be traced to a mutation in a gene called the multi-drug resistance (MDR1) gene, which is needed to form a type of protein that's vital to flushing drugs out of the brain. When this protein is faulty, some drugs, such as ivermectin, remain in the brain where they build up and cause toxic effects.

It's not only ivermectin that causes problems in MDR1 dogs. Other drugs that are known to cause problems in these dogs are:

abamectin, selamectin, milbemycin,and moxidectin (anti-parasite agents used in heartworm, ear mites, mange mites and yard preparations; at doses used to prevent heartworm, these drugs are safe in mutant MDR1 dogs, but at levels used to treat mange, they are not.)

loperamide (antidiarrheal agent found in Imodium; this drug is not safe at normal doses for mutant MDR1 dogs)

acepromazine (tranquilizer; this drug produces deeper and longer sedation in mutant MDR1 dogs; it should only be given at a 75 percent dose in dogs with one copy of the mutant gene, and at 50- to 70 percent doses in dogs with two copies of the mutant MDR1 gene)

butorphanol (analgesic and pre-anesthetic agent; this drug produces deeper and longer sedation in mutant MDR1 dogs; it should only be given at a 75 percent dose in dogs with one copy of the mutant gene, and at 50- to 70 percent dose in dogs with two copies of the mutant MDR1 gene).

vincristine, vinblastineand doxorubicin(chemotherapy agents; this drug is more likely to cause bone marrow suppression and gastrointestinal upset in dogs with the MDR1 mutation; it should be given at 70- to 75 percent normal dose in these dogs. Dogs with one copy of the mutant gene are said to be sensitive; they may have toxic reactions to normal doses of loperamide and some anticancer drugs, and high doses of ivermectin. Dogs with two copies of the mutant gene are said to be super sensitive and are very likely to have toxic reactions to normal doses of loperamide, some anticancer drugs and high doses of ivermectin.

Because several of these drugs are commonly used when your dog has surgery, it's a good idea to find out now if your Collie or Collie relative, or even mixed breed, has the MDR1 gene or genes. Washington State University offers the test, which requires a simple cheek swab and costs about $60. To get a test kit, go to http://www.vetmed.wsu.edu/depts-VCPL/test.aspx

About three out of four collies have the mutant MDR1 gene. The MDR1 mutation is also found in Shetland Sheepdogs, Old English Sheepdogs, German Shepherds, Longhaired Whippets, Silken Windhounds, and a variety of mixed breed dogs, although not as frequently as in Collies.

Researchers are currently seeking cheek swab samples from dogs of the herding breeds, such as Collies and their relatives, that that have experienced unexpected reactions to normal doses of drugs. For more information contact the Veterinary Clinical Pharmacology Lab at Washington State University via e-mail at: VCPL@vetmed.wsu.edu.